Inhaled Corticosteroids on Airway Smooth Muscle in Asthma

NCT ID: NCT00661973

Last Updated: 2019-09-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2011-03-31

Brief Summary

The main objective is to evaluate how treatment with inhaled corticosteroids (ICS) affects the characteristics of airway smooth muscle (ASM) cells from asthmatic subjects. Our hypothesis is that airway smooth muscle cell dysfunction plays an important role in the pathogenesis of asthma, and that treatment with inhaled corticosteroids reverses the abnormalities in airway smooth muscle cell function.

Detailed Description

Aims and Objectives

Most of the work published to date on the effect of steroids on ASM has been carried out in animal models or in in vitro experiments. We would like to evaluate in vivo whether abnormalities in ASM function respond to ICS. Because ASM cells can be obtained from bronchial biopsies obtained via bronchoscopy, we will examine endobronchial biopsies from corticosteroid-naïve, mild asthmatic subjects. In particular, we will examine whether ICS have any effect ASM mass, proliferation and expression of different contractile proteins (α-actin and myosin) and chemokines, and will assess in vitro the response of ASM cells to stimulation by TGF-β and IL-1β. We will also examine the effect of dexamethasone on chemokine release and induced proliferation in vitro before and after treatment with ICS.

We will examine the effect of inhaled corticosteroids in 12 subjects with mild asthma. The subjects will be studied during a baseline period and again after receiving treatment with inhaled corticosteroid therapy with Budesonide Turbohaler (400 ug bd) for 4 weeks. The results of these two periods will be compared.

There will be 5 study visits. In the first two visits, the subjects will undergo spirometry with reversibility testing, a methacholine challenge test, skin prick tests and IgE levels, measurement of exhaled nitric oxide, and subjects will complete an Asthma Control Questionnaire and an Asthma Quality of Life Questionnaire. The third visit will be the day admission for the bronchoscopy. They will be given asthma control diary cards to complete during the 4-week treatment with ICS and receive their ICS turbohaler. At visit 4, they will have repeat spirometry and methacholine challenge to assess if there has been a change secondary to treatment with ICS. The final visit will be for the second bronchoscopy, when the dairy card and ICS inhaler will be collected, and the subjects will complete the Asthma Control and Quality of Life questionnaire.

Conditions

Asthma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

overall

Group Type: EXPERIMENTAL

budesonide

Intervention Type: DRUG

inhaled budesonide (turbohaler) 400 micrograms twice a day for 4 weeks

Interventions

budesonide

inhaled budesonide (turbohaler) 400 micrograms twice a day for 4 weeks

Intervention Type: DRUG

Other Intervention Names

pulmicort

Eligibility Criteria

Inclusion Criteria

• Physician diagnosis of asthma
• Age 18-60
• Intermittent asthma symptoms < once/week
• FEV1>80% of predicted
• Not on inhaled corticosteroid therapy

Exclusion Criteria

• Previous long-term use of inhaled corticosteroids (within 1 year of entry into study)
• Past history of hypersensitivity to budesonide
• Current smokers, or less than 3 years since quitting smoking
• Less than 4 weeks from an exacerbation
• On steroid-sparing agent or immunosuppressant such as azathioprine, methotrexate and ciclosporin
• Concomitant anti-IgE therapy
• Pregnancy
• Previous bronchoscopy within three months of this study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Royal Brompton & Harefield NHS Foundation Trust

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kian F Chung, MBBS FRCP MD DSc

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Asthma lab, Royal Brompton Hospital, Sydney Street

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

07/H0803/239

Identifier Type: -

Identifier Source: secondary_id

2007-006664-29

Identifier Type: -

Identifier Source: org_study_id